A Powerful Chiral Phosphoric Acid Catalyst for Enantioselective Mukaiyama–Mannich Reactions

Abstract

A new BINOL-derived chiral phosphoric acid bearing 2,4,6-trimethyl-3,5-dinitrophenyl substituents at the 3,3'-positions was developed. The utility of this chiral phosphoric acid is demonstrated by a highly enantioselective (ee up to >99 %) and diastereoselective (syn/anti up to >99:1) asymmetric Mukaiyama-Mannich reaction of imines with a wide range of ketene silyl acetals. Moreover, this method was successfully applied to the construction of vicinal tertiary and quaternary stereogenic centers with excellent diastereo- and enantioselectivity. Significantly, BINOL-derived N-triflyl phosphoramide constitutes a complementary catalyst system that allows the title reaction to be applied to more challenging imines without an N-(2-hydroxyphenyl) moiety.

N-Triflylphosphoramides: highly acidic catalysts for asymmetric transformations

“…Zhou and Yamamoto developed an enantioselective Mannich-Mukaiyama reaction (Scheme 49). 126 Using catalyst (S)-NTPA-34, they design a reaction of N-phenyl imines 4.31 and ketene silyl ether 4.32 to furnish anilines 4.33 in good yields and up to 95% ee. This transformation features a carefully designed catalyst.…”

Permanent porous hydrogen-bonded frameworks with two types of Brønsted acid sites for heterogeneous asymmetric catalysis

“…Chiral phosphoric acids derived from axially diols such as 1,1′-binaphthol (BINOL) 41 and 1,1′-spirobiindane-7,7′-diol (SPINOL) 42 have found widespread application as Brønsted acid catalysts in enantioselective transformations involving imines, such as Mannich 43 , Friedel-Crafts (F-C) 44 , Pictet-Spengler 45 , and aza-Diels-Alder reactions 46 . On the other hand, sulfonylcalix[4]arenes react with metal ions to generate a shuttlecock-like tetrametallic cluster, which is an ideal four-connected node in assembling nanosized cages by binding to auxiliary organic linkers 47,48 .…”

N-Vinyl and N-Aryl Hydroxypyridinium Ions: Charge-Activated Catalysts with Electron-Withdrawing Groups

“…Acid-catalyzed reactions are commonplace and are utilized in a wide variety of transformations spanning from the synthesis of small molecules to biocompounds and polymers. The development of Brønsted acids and hydrogen bond-donating organocatalysts, consequently, is of significant interest and a subject of considerable research efforts. , Incorporation of electron-withdrawing groups into these species not only increases their acidities and hydrogen bond donor abilities but also typically leads to more active catalysts and enhanced reaction rates. , Extension of this strategy with the use of one or more positively charged centers was recently reported to be particularly effective in nonpolar solvents, leading to rate accelerations corresponding to orders of magnitude compared to noncharged substituents . Even more active catalysts can be envisioned by introducing electron-withdrawing groups into positively charged substrates.…”